tbuckley/cabot-search huggingface dataset:
Cervical cancer geographical burden analyzer: An interactive, open-access tool for understanding geographical disease burden in patients with recurrent or metastatic cervical cancer.
Authors: Tara Castellano, Christina Washington, Kathleen N. Moore, Yasin Yildiz, Andy Surinach, Jie Ting, Jagpreet Chhatwal, Turgay Ayer
Journal: Journal of Clinical Oncology (2022)

5523 Background: Examining geographic distributions of high and low proportions of recurrent or metastatic cervical cancer (r/mCC) can identify regions with high need of intervention and advance our understanding of r/mCC community-specific risk factors. Previous studies of epidemiologic or geographic clusters in late-stage cervical cancer were conducted prior to the availability of modern treatments for r/mCC. Due to the rapidly evolving treatment landscape for r/mCC use of commercial claims is an important way to follow dynamic practice changes. Our study objective was to understand recent geographical disparities among r/mCC patients in the US. Methods: We developed a web-based tool, Cervical Cancer Geographical Disease Burden Analyzer, that allows users to quantify r/mCC disease burden across metropolitan statistical areas (MSA) over multiple years. The inputs to the web-based tool were extracted through a retrospective analysis of the 2015-2020 MarketScan commercial claims database using a previously validated methodology. We then calculated the r/mCC rate as the ratio of r/mCC cases over cervical cancer (CC) cases for each of the &gt;400 MSA considered. The calculated MSA-specific r/mCC rate was visualized in an interactive US map,. The online interactive tool allowed the users to filter the results by year, age group, and minimum number of diagnoses at the MSA level. Results: Our findings showed that there is large variation with respect to r/mCC disease burden across MSA in the US, with a range of 0-45%. The top five MSA with the highest r/mCC rates from 2018-2020 are presented in the table. In particular, r/mCC rates in Sacremento-Roseville-Arden-Arcade (SRAA), CA and Boston-Cambridge-Newton (BCN), MA were on an increasing trajectory (33% in 2018 to 50% in 2020 in SRAA, CA; and from 41% in 2018 to 50% in 2020 in BCN, MA). On the other hand, while disease burden remained high, we observed decreasing r/mCC rates in Grand Rapids, MI (55% in 2018 and 31% in 2020, resulting in an average r/mCC rate of 42%). Finally, in Cape Coral-Fort Myers, FL and Baltimore-Columbia-Towson, MD the r/mCC rates have fluctuated across time but were consistently &gt;30%. Conclusions: Our web-based online interactive tool can help with identifying areas with high need of intervention, and inform how access, prevention and new or emerging therapies may potentially change the distribution of r/mCC disease burden. To better understand underlying drivers of geographic disparities observed, further efforts should be targeted towards identifying local-level factors. [Table: see text]
Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review
Authors: O T Jones, R N Matin, M van der Schaar, K Prathivadi Bhayankaram, C K I Ranmuthu, M S Islam, D Behiyat, R Boscott, N Calanzani, J Emery, H C Williams, F M Walter
Journal: The Lancet Digital Health (2022)
Barrettʼs esophagus – screening or surveillance, and what about the quality of endoscopy?
Authors: Jan Martinek
Journal: Endoscopy (2022)

Barrettʼs esophagus (BE) is a precancerous condition; the annual risk of developing esophageal adenocarcinoma (EAC) in patients without dysplasia is 0.12 %–0.2 % [1]. Therefore, among 500 to 700 patients with nondysplastic BE, one patient will develop cancer during 1 year of follow-up. Because of this cancer risk, which is however much lower than was historically assumed (1 %–3 %/year), all patients with BE should undergo endoscopic surveillance. The aim of surveillance is the early diagnosis of Barrett’s esophagus-related neoplasia, meaning cancer, and high or low grade dysplasia (HGD/LGD). If diagnosed early, Barrett’s esophagus-related neoplasia can be treated (and cured) using minimally invasive endoscopic treatment, consisting of endoscopic resection techniques (e. g. endoscopic submucosal dissection) or ablation techniques (e. g. radiofrequency ablation). The aim of endoscopic treatment is to eliminate both the neoplasia and the BE.
Aligning mission to digital health strategy in academic medical centers
Authors: Adam B. Cohen, Lisa Stump, Harlan M. Krumholz, Margaret Cartiera, Sanchita Jain, L. Scott Sussman, Allen Hsiao, Walter Lindop, Anita Kuo Ying, Rebecca L. Kaul, Thomas J. Balcezak, Welela Tereffe, Matthew Comerford, Daniel Jacoby, Neema Navai
Journal: npj Digital Medicine (2022)

Abstract The strategies of academic medical centers arise from core values and missions that aim to provide unmatched clinical care, patient experience, research, education, and training. These missions drive nearly all activities. They should also drive digital health activities – and particularly now given the rapid adoption of digital health, marking one of the great transformations of healthcare; increasing pressures on health systems to provide more cost-effective care; the pandemic-accelerated funding and rise of well-funded new entrants and technology giants that provide more convenient forms of care; and a more favorable regulatory and reimbursement landscape to incorporate digital health approaches. As academic medical centers emerge from a pandemic-related reactionary digital health posture, where pressures to adopt more digital health technologies mount, a broad digital health realignment that leverages the strengths of such centers is required to accomplish their missions.
Short-term anthracyclines-induced cardiotoxicity in breast cancer patients.
Authors: Mohammed Alaeddine Saidi, Soumeyya Ghomari
Journal: Journal of Clinical Oncology (2022)

e18703 Background: Anthracycline-containing regimens are effective treatment of early breast cancer; however, they can induce irreversible myocardial damage, leading to significant morbidity and mortality. The main aim of this study was to describe and evaluate early anthracycline cardiotoxicity. Methods: This was a prospective study including breast cancer patients who where candidates for adjuvant anthracycline-based chemotherapy. Patients were assessed at baseline with history, physical exam, standard 12-lead electrocardiography (ECG) and 2D echocardiography, and then shortly after completion of anthracycline-based chemotherapy. We reported the ECG parameters, LVEF calculated using Simpson's biplane method and global longitudinal strain (GLS). Cardiotoxicity was defined as a decline ≥ 5% in LVEF accompanied or not by clinical manifestations of heart failure, or a decline ≥ 10% in GLS. Statistical analysis was performed using SPSS version 26. For comparisons, we used two-tailed Student's t-test. Associations between risk factors and cardiotoxicity were assessed using linear and logistic regression; a p value &lt; 0.05 was considered significant. Results: 171 patients with stage I (10.3%), stage II (81%) or stage III (8.7%) invasive ductal breast carcinoma, with a mean age of 48,1 ± 10 years. Obesity was found in 59 patients and 92 were overweight. Among comorbidities, hypertension was present in 11.7%, diabetes mellitus in 5.2%, and dyslipidemia in 4.6%. The most common concomitant medications were β-blockers in 6.4%, followed by angiotensin II receptor blockers in 5.2%, Statins in 4.6%, biguanides in 5.2%. Cardiac function was assessed 12 ± 7 days before and 19 ± 8 days post chemotherapy. 94 patients received Doxorubicin with a cumulative dose of 240 mg/m2, and 77 received Epirubicin with a cumulative dose of 300 mg/m2. Subclinical Cardiotoxicity was observed in 9 patients (5.2%), defined as a decline ≥ 5% in LVEF and in one patient (0.5%) defined by GLS decline ≥ 10%. This patient had the lowest post-therapy LVEF (40.2%) of the cohort. LVEF and GLS although reduced significantly after treatment, remained within the normal range. (LVEF: 62.8 ± 3% vs. 58 ± 6%, p = 0.03), (GLS: -19.0 ± 2.4% vs. -17.1 ± 1.0%, p = 0.01). Patients receiving Doxorubicin had lower LVEF compared to Epirubicin after therapy (57.1 ± 2% vs. 61.4 ± 2%, p = 0.03). Additionally, we found significant ECG changes in Heart Rate (72.6 ± 11,6 vs. 85.2 ± 14.4 bpm, p = 0.013) and QTc (410.1 ± 24.9 vs. 427.7 ± 26.5 ms, p = 0.032). Cardiotoxicity was not associated with any cardiovascular risk factors. Doxorubicin use was the only risk factor, confirmed on multivariate analysis (p = 0,02). Conclusions: Anthracycline-based chemotherapy has detrimental subclinical effect on electrical activity and left ventricle systolic function in the short term after adjuvant chemotherapy. We did not observe any significant effect of risk factors, it is therefore important to monitor all patients.
ATRT-20. Novel prognostic molecular signatures for improved risk-classification of Atypical Teratoid Rhabdoid Tumours
Authors: Claire Keeling, Yura Grabovska, Patricia O'Hare, Stephen Crosier, Jessica C Pickles, Martina A Finetti, Amy R Fairchild, John Anderson, Darren Hargrave, Bernadette Brennan, Thomas S Jacques, Steven C Clifford, Simon Bailey, Daniel Williamson
Journal: Neuro-Oncology (2022)

Abstract Malignant Rhabdoid Tumours (MRT) are aggressive paediatric malignancies seen in the central nervous system (Atypical Teratoid Rhabdoid Tumours (ATRT)), and kidney and other soft tissues (Extra-cranial Rhabdoid Tumours (ECRT)). With current therapies often proving ineffective and a lack of clear prognostic associations with consensus subgroups, we explored the possibility of using prognostic molecular signatures to further identify the biological characteristics of high risk ATRT patients. By employing a cross-validated feature selection method the methylation profiles of 121 MRT patients were analysed with clinical data to obtain meta-CpG signatures associated with prognosis for ATRT, ECRT and MRT. The relationship between these meta-CpG signatures and the consensus subgroups were further explored, along with the correlation of meta-CpGs with gene expression to establish biological significance. By selecting CpGs for their ability to predict survival this method obtained three novel prognostic methylation signatures which predict MRT outcome (ATRT-5, ECRT-14 and MRT-42). These signatures are independent of molecular subgroup and each signature was significantly associated with overall survival (OS) and event free survival (EFS) in their respective cohorts (p&amp;lt;0.001). Both ATRT-5 and MRT-42 maintained their significant association with OS in an independent ATRT cohort (n=64) and each meta-CPG signature is prognostically independent of other major clinical risk factors (e.g. receipt of radiotherapy and presence of metastases). Biologically, individuals with high-risk methylation signatures showed a gene expression profile suggestive of higher proliferative rates and tumours with low-risk scores in ATRT-5 and MRT-42 had an upregulated inflammatory response and increased immune infiltration. Combining these meta-CpGs with other significant clinical risk-factors produced high performing multivariate Cox-models enabling us to propose new stratification models for ATRT and MRT patients. These subgroup-independent prognostic signatures represent a distinct biology in ATRT and, if validated in prospective studies, could progress the use and efficacy of precision-based medicine in this therapeutically challenging disease.
Chemotherapy is superior to checkpoint inhibitors after radical surgery for urothelial carcinoma: A systematic review and network meta-analysis of oncologic and toxicity outcomes
Authors: E. Laukhtina, R. Sari Motlagh, K. Mori, S. Katayama, P. Rajwa, T. Yanagisawa, F. Quhal, H. Mostafaei, N.С. Grossmann, F. König, A. Aydh, B. Pradere, I. Resch, A.S. Merseburger, D. Enikeev, S.F. Shariat
Journal: European Urology (2022)
Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications
Authors: Maciej Tomaszewski, Andrew P. Morris, Joanna M.M. Howson, Nora Franceschini, James M. Eales, Xiaoguang Xu, Sergey Dikalov, Tomasz J. Guzik, Benjamin D. Humphreys, Stephen Harrap, Fadi J. Charchar
Journal: Kidney International (2022)

Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage.
Xpert® bc detection as a diagnostic tool in upper urinary tract urothelial carcinoma: Preliminary results
Authors: C. D'Elia, E. Trenti, P. Krause, A. Pycha, C. Mian, C. Schwienbacher, E. Hanspeter, M. Kafka, M. Palermo, G.A. Spedicato, S. Holl, A. Pycha
Journal: European Urology (2022)
Novel mitochondria-targeting compounds selectively kill human leukemia cells
Authors: Svetlana B. Panina, Jingqi Pei, Natalia Baran, Elissa Tjahjono, Shraddha Patel, Gheath Alatrash, Sergej Konoplev, Leonid A. Stolbov, Vladimir V. Poroikov, Marina Konopleva, Natalia V. Kirienko
Journal: Leukemia (2022)
Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial
Authors: Irene L. M. Reijers, Alexander M. Menzies, Alexander C. J. van Akkooi, Judith M. Versluis, Noëlle M. J. van den Heuvel, Robyn P. M. Saw, Thomas E. Pennington, Ellen Kapiteijn, Astrid A. M. van der Veldt, Karijn P. M. Suijkerbuijk, Geke A. P. Hospers, Elisa A. Rozeman, Willem M. C. Klop, Winan J. van Houdt, Karolina Sikorska, Jos A. van der Hage, Dirk J. Grünhagen, Michel W. Wouters, Arjen J. Witkamp, Charlotte L. Zuur, Judith M. Lijnsvelt, Alejandro Torres Acosta, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Katarzyna Jóźwiak, Carolien Bierman, Kerwin F. Shannon, Sydney Ch’ng, Andrew J. Colebatch, Andrew J. Spillane, John B. A. G. Haanen, Robert V. Rawson, Bart A. van de Wiel, Lonneke V. van de Poll-Franse, Richard A. Scolyer, Annelies H. Boekhout, Georgina V. Long, Christian U. Blank
Journal: Nature Medicine (2022)
A feasibility study of the therapeutic response and durability of short-term androgen targeted therapy in early prostate cancer managed by surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) study
Authors: T. Barrett, S. Pacey, K. Leonard, J. Wulff, I.-G. Funingana, V.J. Gnanapragasam
Journal: European Urology (2022)
Using T stage to predict outcomes of adjuvant oxaliplatin (OX)-based chemotherapy (CT) in stage III colon cancer (CC): An ACCENT pooled analysis.
Authors: Romain Cohen, Morteza Raeisi, Greg Yothers, Hans-Joachim Schmoll, Daniel G. Haller, Jean-Baptiste Bachet, Benoist Chibaudel, Norman Wolmark, Takayuki Yoshino, Richard M. Goldberg, Rachel Kerr, Sara Lonardi, Thomas J. George, Einat Shacham Shmueli, Lama Sharara, Thierry Andre, Qian Shi, Aimery De Gramont
Journal: Journal of Clinical Oncology (2022)

3606 Background: Standard adjuvant CT for stage III CC are FOLFOX and CAPOX. Recently, IDEA study separated stage III patients (pts) into low risk (T1 to 3, N1) and high risk (T4 or N2). We recently confirmed benefit of OX in both risk groups. However, we observed a difference in the two high-risk subgroups, with benefit in N2 but not in T4 (Margalit O et al; Clin Colorectal Cancer 2021). This prompted us to compare outcomes (OS/TTR) between treatment with OX vs. without OX within sub-stage III CC groups defined by T and N. Methods: We pooled 4941 stage III CC pts from the three studies evaluating 6 months of CT with fluoropyrimidine (FP) ± OX: MOSAIC, C-07 and XELOXA. Baseline characteristics were compared using χ 2 and t-test. OS was compared between OX and no OX in T and N subgroups. Kaplan-Meier analyses, adjusted and unadjusted Cox models stratified by study were used. Sub-groups classification was done according to OX benefit and verified by interaction test (Int) considered as significant with a P&lt;0.1. We considered for recommendation of using OX-based adjuvant CT, 1) significant benefit in OS, 2) significant Int between substage and adjuvant therapy, and 3) the three individual trials showing similar results (benefit or non-benefit of OX). Results: In stage III population, T3 pts were 74.9%, T1-2 12.4%, T4 13.1%, while N stage was N1 64.7% and N2 35.3%. Population was well balanced according to treatment allocation in most subgroups. A significant benefit of OX was only observed in T3N1 and T3N2 (OS HR 0.76). Whatever N stage, there was no significant benefit of OX in the T1-2 and T4 subgroups. The effect of OX+FP vs FP alone in OS of the three studies differed between T3 and T1-2 subgroups (P = 0.047). Interaction was borderline between T3 and T4 subgroups (P = 0.10) but there was no interaction between T1-2 and T4 subgroups (P = 0.429). A benefit of OX in TTR remained in the T4 population. Discrepancy between advantage in time to relapse (TTR) and no advantage in OS was not explained by survival post relapse. Conclusions: Our analysis suggested that pts with T1-2N1-2 and T4N1-2 disease had no OS benefit of addition of OX to FP. The good survival achieved with FP alone in T1-2N1-2 pts (5-yr OS 89%) question the addition of OX. In the T4 population our results suggested that benefit of OX was limited and that further studies should assess this issue or at least stratify pts on T stage in the future adjuvant trials in CC. [Table: see text]
Reducing SARS-CoV-2 in Shared Indoor Air
Authors: Deborah Dowell, William G. Lindsley, John T. Brooks
Journal: JAMA (2022)

Reducing SARS-CoV-2 in Shared Indoor Air SARS-CoV-2 replicates in the respiratory tract and spreads through exhalation of infectious respiratory particles.The chances of transmission increase the longer an uninfected person stays in an enclosed space with an infected person.Infection can occur not only through short-range transmission of exhaled respiratory particles from an infectious person resulting in mucous membrane deposition or inhalation of exhaled respiratory particles by an uninfected person.Infection also can occur through long-range transmission from inhalation of infectious respiratory particles that remain suspended in air for longer periods (potentially after the infectious person is no longer present) and across longer distances (greater than a few meters).Because no single approach is 100% effective in preventing COVID-19, prevention measures work best when layered, including vaccination and nonpharmacologic interventions that reduce inhalation of infectious particles.Community masking and physical distancing, both of which can reduce the likelihood of encountering and inhaling virus-containing particles, have received substantial attention.However, there is less public awareness about existing indoor air recommendations that
Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.
Authors: Christopher Gates, Carl Shultz, William Phillip Petros, Sijin Wen, Don Primerano, Lori Hazlehurst, Jim Denvir, Konstantinos Sdrimas
Journal: Journal of Clinical Oncology (2022)

e19022 Background: Many previous population health studies examining adults with acute myeloid leukemia (AML) are derived from national databases within large urban centers. To address the concern of under-representation of rural Appalachian population in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML. As the only stem cell transplantation center in the state, WVU is uniquely situated to capture most of these patients from the state and surrounding area. Due to its unique industry and environmental exposures, we hypothesized that WV may have both different rates of mutations and differing outcomes than the nation as a whole. Methods: We performed whole exome sequencing on 26 patients with newly diagnosed AML from paired bone marrow and buccal samples that were obtained from 2015 to 2017. Whole exome sequencing libraries were prepared using Agilent SureSelect Human Whole Exome technology. The libraries were sequenced on an Illumina HiSeq1500 sequencer using paired end runs. Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. Variables measured included association between biomarker data and progression-free survival (PFS) and overall survival (OS). Results: Median patient age was 68 years and women represented 10 of the patients (37%). Twenty-one patients had de novo AML (84%), 3 patients had preceding MDS (12%), and 1 patient had therapy-related AML (4%). As per ELN criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant with the following donors: 4 MUD (50%), DUCB (37.5%), and 1 haploidentical (12.5%). The median PFS and OS were 16.5 months and 26.6 months, respectively. Tobacco use was the largest known exposure with 7 patients. We noted a similar mutational trend compared to national TCGA data, except for an increased tumor mutation burden and higher frequency of the following mutations as seen in Table. Neither MUC3A or MUC5AC were identified in the TCGA database. Of our five patients with BCOR mutations, two had a co-existing FLT3-ITD mutation, one of which also had a NPM1 mutation. Two patients had secondary AML, while the other 3 had de novo disease. The median OS was 63 days. While not statistically significant, BCOR mutation was trending toward a poor prognostic indicator.Conclusions: Despite our small patient cohort, the findings provide further assessment of predisposing detrimental mutations in AML in the Appalachian region and associated survival outcomes.[Table: see text]